Contraction of vascular smooth muscle in the walls of blood vessels can decrease blood flow to a tissue or cause an elevation of blood pressure. Biochemical studies on myosin isolated from smooth muscle have shown that one of the small subunits (light chains) can be phosphorylated by a specific enzyme found in smooth muscle. Based on these studies, myosin light chain phosphorylation has been proposed as the only determinant of whether smooth muscle contracts or relaxes. We showed that phosphorylation occurred under more physiological conditions, during contraction of intact smooth muscle but that it was not simply correlated with force. During prolonged contractions of hog carotid artery strips, force was maintained, but phosphorylation and maximum shortening velocity declined, leading us to suggest that phosphorylation regulated the cycling rate of crossbridges (and therefore velocity), but not the number of crossbridges developing force. Dephosphorylation of attached crossbridges was postulated to create a non-cycling "latchbridge" which maintains force economically. Our long term goal is to understand how a specific biochemical property, myosin light chain phosphorylation, is related to the regulation of contraction under physiological conditions in arterial smooth muscle. To achieve this goal we propose to perform sophisticated mechanical studies of intact and "skinned" preparations under conditions where the extent of phosphorylation (or thiophosphorylation) can be controlled independently of the Ca++ concentration. This will allow the individual effect of Ca++ and phosphorylation to be measured on the following mechanical properties: force development, muscle stiffness, shortening velocity, Ca++ dependent resistance to stretch, stress relaxation rate, and isometric relaxation rate. Experiments are also proposed to study the role of phosphorylation in the regulation of histamine--induced rhythmic contraction of carotid artery strips. We also propose comparative studies on arteries of hypertensive and normal dogs, and mathematical modelling of the mechanical responses of intact arteries. The proposed experiments should provide valuable insights into the regulatory mechanisms of vascular smooth muscle.